Direct induction of complement activation by pharmacologic activation of plasminogen

Background Complement activation occurs in patients with myocardial infarction treated with fibrinolytic agents and plays a critical role in reperfusion injury, This study was designed to determine whether pharmacologic activation of plasminogen directly induces complement activations. Methods Whole blood was incubated with plasminogen activators and the plasma was assayed for C3a levels as an indicator of complement activation, Results Therapeutic concentrations of tissue-type plasminogen activator, streptokinase, or urokinase increased C3a concentrations from a baseline of approximately 500 ng/ml to an average of 1300-1500 ng/ml with tissue-type plasminogen activator or urokinase, and to an average of approximately 4000 ng/ml with streptokinase (P<0.01, versus baseline for all plasminogen activators). Plasminogen activation also enhanced complement activation induced by conventional complement activators. Conclusions These results indicate that pharmacologic plasminogen activation may exacerbate reperfusion injury either by directly inducing complement activation or by enhancing the activation initiated by other mechanisms, or both.